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ACTRIMS 2023 | Molecular mechanisms associated with MS progression, severity and phenotype

Peter Kosa, PhD, National Institutes of Health, Bethesda, MD, describes a study to identify pathways and upstream regulators that correlate with all measurable aspects of multiple sclerosis (MS) phenotype and develop and validate CSF biomarker-based models predicting disability and severity outcomes. Over 5000 protein data were analyzed in CSF samples of relapsing-remitting and progressive MS patients and healthy controls, along with nine prospectively acquired outcomes of severity and disability. CSF proteins significantly correlated with the MS outcomes were evaluated by Ingenuity Pathway Analysis to uncover MS-related biology. Neuroinflammation and fibrosis were two pathways identified as associated with MS progression. Interestingly, localization of the CNS injury showed distinct molecular signatures. While patients with predominant brain injury showed proportionally higher levels of neuroinflammation, spinal cord involvement was reflected by increased fibrosis and tissue hypoxia. Additionally, machine learning algorithms were used to generate and independently validate CSF protein-based models predicting MS outcomes. This interview took place at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2023 in San Diego, CA.

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